CN116354912B - Compound and application thereof in serving as or preparing ABCG2 agonist - Google Patents

Compound and application thereof in serving as or preparing ABCG2 agonist Download PDF

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CN116354912B
CN116354912B CN202111616319.3A CN202111616319A CN116354912B CN 116354912 B CN116354912 B CN 116354912B CN 202111616319 A CN202111616319 A CN 202111616319A CN 116354912 B CN116354912 B CN 116354912B
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agonist
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CN116354912A (en
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徐愿坚
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Hangzhou Yijian Biomedical Technology Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The invention belongs to the field of medicines or health products, and particularly relates to a compound and application thereof in serving as or preparing an ABCG2 agonist. The compound (shown in the formula I or the formula II) and enantiomer, diastereoisomer, salt, ester, prodrug, solvate or solvate of the salt thereof can obviously reduce creatinine level and improve renal function of mice when being used as or used for preparing the ABCG2 agonist.

Description

Compound and application thereof in serving as or preparing ABCG2 agonist
Technical Field
The invention belongs to the field of medicines, and particularly relates to a compound and application thereof in serving as or preparing an ABCG2 agonist.
Background
Creatinine (Cre) is the product of exogenous animal muscle or human muscle after metabolism in human body, and has chemical formula of C 4 H 7 N 3 O, 1mg of creatinine can be produced per 20g of muscle metabolism. Creatinine is transported through the blood and eventually is removed from the body primarily by glomerular filtration. The concentration of creatinine in serum is relatively constant in vivo when the meat intake is stable and there is no substantial change in muscle metabolism of the body. Creatinine is an important indicator of kidney function. The upper limit of normal serum creatinine concentration in humans is 133umol/L, which is indicated as inflammatory injury phase when the serum creatinine concentration exceeds 133umol/L, as renal function injury phase when the serum creatinine concentration exceeds 186umol/L, as renal failure phase when the serum creatinine concentration exceeds 451umol/L, and as uremia when the serum creatinine concentration exceeds 707 umol/L.
Kidneys are important organs for excreting urine, waste and poison. Many factors may lead to impairment of renal function, with the effects of digestive metabolic diseases being particularly pronounced, such as diabetes, hyperuricemia, etc. Recent studies indicate that the adenosine triphosphate binding cassette transporter G2 (Adenosine triphosphate binding cassette transporter G, ABCG 2) is involved in renal excretion function, and that ABCG2 export is expressed in the intestinal tract and apical membrane of the kidney, exerting excretion function. Therefore, ABCG2 is an important drug target for preventing and treating injury to renal function.
Herba Lycopi (Eupatorium lindleyanum DC.) is a plant name of herba Eupatorii Lindleyani, a perennial herb, in Jiangsu district. The Chinese medicine herba Eupatorii Lindleyani has bitter taste, and has effects of relieving cough, clearing heat and toxic materials, promoting urination, detumescence, and lowering blood pressure, and is suitable for common cold, cough with excessive phlegm, headache, tonsillitis, bacillary dysentery, and hypertension. Lindley eupatorium is commonly used for treating chronic tracheitis, bronchitis, hypertension and the like in clinic. The branch and leaf are used as medicine for relieving exterior syndrome, eliminating dampness, regulating middle warmer, and eliminating dampness, and can be used for treating cough due to fatigue, hematemesis, hemoptysis, stranguria with turbid urine, leucorrhea, and innominate swelling and pain.
The modern pharmaceutical research shows that the active ingredients in the lycopus herb mainly comprise more than ten hundred compounds such as volatile oil, organic acids, triterpenes, sesquiterpenes, trace elements and the like. Among them, the guaiane type sesquiterpenoids are considered as a compound with remarkable biological activity, and no related literature records that the guaiane type sesquiterpenoids can act on an ABCG2 target or reduce serum creatinine concentration after searching.
Disclosure of Invention
Therefore, the invention provides a compound which can act on the target point of the ABCG2 medicine through researching the guaiane sesquiterpene compound, and the compound can improve the expression of the ABCG2 in brush-like border membranes and intestinal tracts of kidney nearly Qu Xiao, enhance the discharge of creatinine from the body, reduce serum creatinine level and further repair renal functions.
The structural formula of the compound is shown as formula I or formula II:
wherein R is 1 、R 2 、R 3 、R 4 、R 5 、R 6 Independently of each other, selected from hydrogen, hydroxy, methoxy, acetyl.
Specifically, the compound shown in formula I has the same lactone structure as guaiane sesquiterpene compound, and the only difference is R 1 、R 2 、R 3 The three substituents are different; represented by formula IIThe compounds differ from formula I in the configuration of the double bond on the macrocycle.
Preferably, the compound of formula I or formula II is selected from the group consisting of compounds of formula III, formula IV, formula V, formula VI, formula VII, formula VIII, formula IX, and formula X;
the invention also aims to provide application of the compound and enantiomer, diastereoisomer, salt, ester, prodrug, solvate or solvate of salt thereof in serving as or preparing an ABCG2 agonist.
The invention also aims to provide application of the compound and enantiomer, diastereoisomer, salt, ester, prodrug, solvate or solvate of salt thereof in preparing medicines with creatinine reducing effect.
The invention also aims to provide application of the compound and enantiomer, diastereoisomer, salt, ester, prodrug, solvate or solvate of salt thereof in preparing medicines for preventing and treating renal function injury.
The invention further provides a preparation method of the compound shown in the formula III, the formula IV or the formula V, wherein the content of the compound shown in the formula III or the formula IV in the guaiane type sesquiterpene compound in the eupatorium adenophorum is extremely low, and the total abundance of the guaiane type sesquiterpene compound in the eupatorium adenophorum is as high as 1% -3%, so that the compound has extraction and separation values. Based on the method, on the basis of the traditional method for extracting and analyzing the lindley eupatorium herb hemiterpenoid, a directional hydrolysis method and a high-efficiency countercurrent chromatography method are added, so that the yield of the target compound is improved from 0.0003-0.0005% to 0.3-1%, and the purity is over 95%.
The method comprises the following steps:
(1) Reflux extracting herba Lycopi herb with methanol or ethanol to obtain extractive solution, removing wax, and concentrating with chloroform or dichloromethane to obtain extract;
(2) Separating the extract by using macroporous resin, eluting with ethanol water solution, collecting 40-60% of components by volume percent of the ethanol water solution, concentrating and drying to obtain hydrolysis raw materials;
(3) Dissolving the hydrolysis raw material in methanol or ethanol, and then hydrolyzing in an acid environment to obtain a hydrolysis crude product solution;
(4) Separating the hydrolyzed crude product solution by macroporous resin, eluting by ethanol and water to obtain eluent, wherein the volume percentage of the ethanol is 0-100%; concentrating and drying eluent obtained when the volume percentage of ethanol is 15-25%, and separating and purifying by adopting high-efficiency countercurrent chromatography to obtain the compounds shown in the formulas III, IV and V.
Further, in the step (3), the pH value of the acidic environment is 0.1-2.
Further, in the step (3), the temperature of the hydrolysis is 0-65 ℃.
Further, in the step (3), the pH value is adjusted by using concentrated sulfuric acid or concentrated hydrochloric acid or phosphoric acid.
Further, in the step (3), the hydrolysis reaction time is 8-72 hours.
Specifically, in the step (4), separating and purifying the hydrolyzed crude product solution by adopting a high-efficiency countercurrent chromatography ethyl acetate and water solvent system, using an ethyl acetate layer as a stationary phase and a water layer as a mobile phase, and collecting eluent in a column volume period of 0.9-1.1 to obtain a compound shown in a formula III; collecting the eluent in 1.4-1.6 column volume time periods to obtain the compound shown in the formula IV; separating and purifying with high performance countercurrent chromatography dichloromethane, water and methanol (1:1:1) solvent system, collecting eluent of 1.9-2.1 column volume time period with upper phase as stationary phase and lower phase as mobile phase, concentrating by rotary evaporation, and lyophilizing to obtain compound shown in formula V.
Specifically, the method for preparing the compound shown in the formula III or the formula IV comprises the following steps:
(1) Extracting. Collecting dried whole plant of herba Lycopi, pulverizing, reflux extracting with 90% methanol or ethanol, concentrating the extractive solution, removing wax with petroleum ether, adding water and chloroform or dichloromethane, extracting water layer with chloroform or dichloromethane for 2-3 times, concentrating chloroform or dichloromethane layer, and drying to obtain extract;
(2) Removing impurities. Separating the extract with AB-8 macroporous resin, eluting with ethanol water solvent, mixing the components between 40% -60% ethanol, concentrating, and drying to obtain hydrolysis raw material;
(3) And (5) hydrolyzing. Dissolving the hydrolysis raw material in 90% methanol or ethanol, adding concentrated sulfuric acid or concentrated hydrochloric acid or phosphoric acid, adjusting the pH value to be between 0.1 and 2.0, and hydrolyzing for 8 to 72 hours at the temperature of between 0 and 65 ℃ to obtain a hydrolysis crude product solution;
(4) And (5) separating and purifying. Separating and purifying the hydrolyzed crude product solution by adopting a high-efficiency countercurrent chromatography ethyl acetate and water solvent system, using an ethyl acetate layer as a stationary phase and a water layer as a mobile phase, and collecting eluent in a column volume period of 0.9-1.1 to obtain a compound shown in a formula III; collecting the eluent in 1.4-1.6 column volume time periods to obtain the compound shown in the formula IV.
In the present invention, "drug" includes oral dosage forms or injection dosage forms, the oral dosage forms are the following dosage forms: tablets, powders, granules, tea, capsules, soft capsules, oral liquid, pills, ointment and wine; the injection is injection.
In the invention, if the compound is used for preparing medicines, the compound is taken as an active substance, and then auxiliary materials for medicaments are added to prepare medicines.
The invention has the beneficial effects that
The invention provides a compound capable of exciting ABCG2 transporter, which can obviously reduce creatinine level and improve renal function of mice through the embodiment.
Drawings
FIG. 1 shows the results of various mouse model tests (administration concentration: 20 mg/kg).
Detailed Description
The examples are presented for better illustration of the invention, but the invention is not limited to the examples. Those skilled in the art will appreciate that various modifications and adaptations of the embodiments described above are possible in light of the above teachings and are intended to be within the scope of the invention.
In an embodiment of the present invention, an apparatus includes: API 4000 triple quadrupole LC-MS/MS Mass Spectrometry System (ABSCIEX Co., USA); LC-30AD ultra high performance liquid System (Shimadzu Corp.); R21G type high-speed refrigerated centrifuge (japanese Hitachi Co.); elix10 ultra pure water purification system (millpoer, usa); XS-105 parts per million precision electronic balance (METTLER toldo company, switzerland).
In an embodiment of the present invention, the reagent comprises: formic acid (Formic acid, sigma-Aldrich, batch No. 56302-10 ML) acetonitrile and methanol were all chromatographically pure (Merck, germany), and water was ultrapure water.
In the examples of the present invention, the chromatographic conditions in LC-MS/MS detection are shown in Table 1:
TABLE 1 LC-MS/MS detection chromatographic conditions
TABLE 2 LC-MS/MS detection gradient elution procedure
Time (min) A (5 mM ammonium acetate (0.1% formic acid)) B (acetonitrile)
0.1 98 2
3.5 98 2
4 10 90
6.5 10 90
7 98 2
10 98 2
In the embodiment of the invention, mass spectrum conditions in LC-MS/MS detection are as follows: using MRM mode, gas1:30psi, gas2:50psi, IS:5500v, tem:500 ℃, CAD:4psi, CUR:15Psi, ion pairs are shown in Table 3 below:
TABLE 3LC-MS/MS detection Mass Spectrometry ion pairs and other conditions
Sequence number Ion pair Name of the name DP CE CXP Scan mode
1 114.1/85.9 Cre 80 15 20 Positive
In the embodiment of the invention, the preparation of the standard solution is as follows: accurately weighing the creatinine standard 10.82 and m g, placing the creatinine standard 10.82 and m g into a 10mL volumetric flask, adding water for dissolution, and fixing the volume to 10mL to obtain the creatinine standard stock solution of 1.082 mg/mL. And storing the mixture in a refrigerator at the temperature of 4 ℃ until the mixture is used.
In the embodiment of the invention, the blank serum sample treatment method comprises the following steps: precisely removing 50 mu L of mixed blank serum sample, precisely adding 10 mu L of water, adding 400 mu L of methanol after vortex mixing for 30s, vortex mixing for 1min, centrifuging at 12000rpm for 15min, taking 100 mu L of supernatant, and carrying out sample injection analysis at 2 mu L.
In the embodiment of the invention, the preparation and treatment of the drug-containing serum are as follows: 50uL of drug-containing serum is precisely sucked into a 1.5mL EP tube, 400 uL of methanol is added, the mixture is uniformly mixed by vortex for 1min and centrifuged at 12000rpm for 15min, 100 uL of supernatant is taken into a sample injection bottle, and 2 uL of supernatant is subjected to sample injection analysis.
In the embodiment of the invention, an ABCG2 agonist, named as an "agonist A", is prepared, and the structural formula of the compound is as follows:
in the embodiment of the invention, an ABCG2 agonist, named as an "agonist B", is prepared, and the structural formula of the compound is as follows:
in the embodiment of the invention, an ABCG2 agonist, named as an agonist C, is prepared, and the structural formula of the compound is as follows:
example 1
(1) Extracting by taking 800g of the whole plant of Eupatorium adenophorum, pulverizing, and reflux-extracting with 90% ethanol with volume 5 times; concentrating the extractive solution by rotary evaporation, and removing wax with petroleum ether; then adding 5 times of water and 3 times of dichloromethane into the rest part, separating and recovering a dichloromethane layer by using a separating funnel, extracting a water layer by using dichloromethane for 3 times, combining the collected dichloromethane solution, evaporating, concentrating and drying to obtain 69g of extract;
(2) Removing impurities, separating the extract with AB-8 macroporous resin, eluting with ethanol-water (100:0-0:100), mixing the components between 40% -60% ethanol, concentrating, and drying to obtain 14g hydrolysis raw material;
(3) Hydrolysis, namely dissolving the hydrolysis raw material in 90% methanol, then adjusting the pH value to 1.3 by using concentrated sulfuric acid, and hydrolyzing in a water bath kettle at the temperature of 60+/-1 ℃ for 60 hours to obtain a crude product solution;
(4) Separating and purifying by separating the crude product solution with AB-8 macroporous resin, eluting with ethanol-water (100:0-0:100), collecting 15% ethanol-eluted component and 25% ethanol-eluted component, concentrating and drying respectively; separating and purifying the 15% ethanol eluting component by adopting a high-efficiency countercurrent chromatography ethyl acetate and water solvent system, taking a water layer as a stationary phase and an ethyl acetate layer as a mobile phase, collecting eluent in a column volume period of 0.9-1.1, and freeze-drying to obtain 1.76g of agonist A with the purity of 96%; separating and purifying the 25% ethanol eluting component by adopting a high-efficiency countercurrent chromatography ethyl acetate and aqueous solution system, collecting eluent with the column volume time of 1.4-1.6 by taking an ethyl acetate layer as a stationary phase and a water layer as a mobile phase, and freeze-drying to obtain 2.81g of the agonist B with the purity of 95%; A. the total yield of both compounds B was 0.571%.
Example 2
(1) Extracting: taking 1500g of the whole plant of lycopus herb, crushing, and extracting with 90% ethanol with the volume of 3 times under reflux; concentrating the extractive solution by rotary evaporation, and removing wax with petroleum ether; then adding 4 times of water and 2 times of dichloromethane into the rest part, separating and recovering a dichloromethane layer by using a separating funnel, extracting a water layer by using dichloromethane for 3 times, combining the collected dichloromethane solution, evaporating, concentrating and drying to obtain 115g of extract;
(2) Removing impurities: separating the extract with AB-8 macroporous resin, eluting with ethanol-water (100:0-0:100), mixing the components between 40% -60% ethanol, concentrating, and drying to obtain 23g hydrolysis raw material;
(3) Hydrolysis: dissolving the hydrolysis raw material in 90% methanol, then regulating the pH value to 0.8 by phosphoric acid, and hydrolyzing in a water bath kettle at 58+/-1 ℃ for 72 hours to obtain a crude product solution;
(4) And (3) separating and purifying: separating the crude product solution with AB-8 macroporous resin, eluting with ethanol-water (100:0-0:100), collecting 15% ethanol-eluted component and 25% ethanol-eluted component, concentrating and drying respectively; separating and purifying the 15% ethanol eluting component by adopting a high-efficiency countercurrent chromatography ethyl acetate and water solvent system, collecting eluent with the column volume time of 0.9-1.1 by taking an ethyl acetate layer as a stationary phase and a water layer as a mobile phase, and freeze-drying to obtain 3.27g of the agonist A with the purity of 97%; separating and purifying 25% ethanol eluting component by adopting high performance countercurrent chromatography ethyl acetate and aqueous solution system, collecting eluent of 1.4-1.6 column volume time periods by using ethyl acetate layer as stationary phase and water layer as mobile phase, and lyophilizing to obtain 4.39g of agonist B with purity of 96%; A. the total yield of both compounds B was 0.511%.
Example 3
(1) Extracting: taking 2000g of the whole plant of lycopus herb, crushing, and extracting with 90% ethanol with the volume of 3 times under reflux; concentrating the extractive solution by rotary evaporation, and removing wax with petroleum ether; then adding 4 times of water and 2 times of dichloromethane into the rest part, separating and recovering a dichloromethane layer by using a separating funnel, extracting a water layer by using dichloromethane for 3 times, combining the collected dichloromethane solution, evaporating, concentrating and drying to obtain 135g of extract;
(2) Removing impurities: separating the extract with AB-8 macroporous resin, eluting with ethanol-water (100:0-0:100), mixing the components between 40% -60% ethanol, concentrating, and drying to obtain 30g hydrolysis raw material;
(3) Hydrolysis: dissolving the hydrolysis raw material in 90% methanol, then adjusting the pH value to 0.8 by using concentrated hydrochloric acid, and hydrolyzing in a water bath kettle at a temperature of 50+/-1 ℃ for 24 hours to obtain a crude product solution;
(4) And (3) separating and purifying: separating the crude product solution with AB-8 macroporous resin, eluting with ethanol-water (100:0-0:100), collecting 20% ethanol-eluted component, concentrating, and drying; separating and purifying by high performance countercurrent chromatography with dichloromethane, water and methanol (1:1:1) solvent system, collecting eluent of 1.9-2.1 column volume time periods by using upper phase as stationary phase and lower phase as mobile phase, concentrating by rotary evaporation, and lyophilizing to obtain 6.18g of agonist C with purity of 98% and total yield of 0.309%.
Example 4 Effect verification
(1) Selecting 50 qualified six-month-old mice, wherein the weight of each mouse is 20+/-3 g, and the mice are adaptively raised for 1 week under the environment of intermittent illumination every 12 hours at the temperature of 24+/-2 ℃ and the relative humidity of 55+/-5%. Thereafter, the mice were randomized into 5 groups, high creatinine model group, blank group, agonist a group, agonist B group, and agonist C group, respectively.
(2) D-galactose is adopted to induce kidney aging of mice, 200mg/kg of D-galactose is injected subcutaneously through the nape of the neck, the administration is carried out for 1 time a day, the continuous administration is carried out for 8 weeks, the induction of hypercreatinine is carried out, and the administration concentrations of agonist A, agonist B and agonist C are 20mg/kg from the 4 th week of molding; the model group is infused with physiological saline; blank groups are non-molded mice, the molded injection agent is replaced by normal saline, and the oral medicine is also infused with normal saline.
(3) The serum creatinine concentrations of the blank experimental group, the high creatinine model experimental group, the agonist A experimental group, the agonist B experimental group and the agonist C experimental group are detected by adopting LC-MS/MS analysis, the results are shown in figure 1, and the experimental results show that:
agonist A reduced serum creatinine concentration from 16.3mg/L to 5.79mg/L in kidney injured mice, below the blank (6.31 mg/L), indicating that agonist A can significantly reduce creatinine levels and improve kidney function in mice.
The mice model test was carried out using agonist B at a concentration of 20mg/kg. Experimental results show that the serum creatinine concentration of the agonist B in the kidney injury mice is reduced from 16.3mg/L to 3.25mg/L, which is lower than that of a blank group (6.31 mg/L), and the effect of the agonist B is better than that of the agonist A and the creatinine reducing effect is better.
The mice model test was carried out using agonist C at a concentration of 20mg/kg. The experimental result shows that the serum creatinine concentration of the agonist C in the kidney injury mice is reduced from 16.3mg/L to 6.48mg/L, which is slightly higher than that of a blank group (6.31 mg/L), and the agonist C has obvious effect of reducing the serum creatinine concentration although the agonist C is inferior to the agonist A and the agonist B.
Finally, it is noted that the above embodiments are only for illustrating the technical solution of the present invention and not for limiting the same, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications and equivalents may be made thereto without departing from the spirit and scope of the technical solution of the present invention, which is intended to be covered by the scope of the claims of the present invention.

Claims (4)

1. The application of the compound in preparing the medicament with the creatinine reducing effect is characterized in that the structural formula of the compound is shown as a formula III, a formula IV or a formula V,
2. the use according to claim 1, wherein the medicament comprises an oral dosage form or an injectable dosage form, the oral dosage form being of the following: tablets, powders, granules, capsules, oral liquid, pills and paste; the injection is injection.
3. Use of a compound for the manufacture of a medicament for the prevention and treatment of impaired renal function, wherein the compound prevents and treats impaired renal function by reducing serum creatinine concentration; the structural formula of the compound is shown in a formula III, a formula IV or a formula V,
4. the preparation method of the compound shown in the formula III, the formula IV or the formula V is characterized in that the structural formula of the compound shown in the formula III, the formula IV or the formula V is as follows:
the method comprises the following steps: (1) Reflux extracting herba Lycopi herb with methanol or ethanol to obtain extractive solution, removing wax from the extractive solution, and concentrating with dichloromethane to obtain extract; (2) Separating the extract by using AB-8 macroporous resin, eluting with ethanol water solution, collecting 40% -60% components by volume of the ethanol water solution, concentrating and drying to obtain hydrolysis raw materials; (3) Dissolving the hydrolysis raw material in methanol or ethanol, and then hydrolyzing in an acid environment to obtain a hydrolysis crude product solution; the pH value of the acidic environment is 0.1-2; the temperature of the hydrolysis is 50-65 ℃; (4) Separating the hydrolyzed crude product solution by using AB-8 macroporous resin, eluting by using ethanol and water to obtain eluent, wherein the volume percentage of the ethanol is 0-100%, and the volume percentage of the ethanol and the water is 100:0-0:100; concentrating and drying eluent obtained when the volume percentage of ethanol is 15-25%, and separating and purifying by adopting high-efficiency countercurrent chromatography to obtain the compounds shown in the formulas III, IV and V; in the high-efficiency countercurrent chromatography, the solvent system of the compounds shown in the formulas III and IV comprises ethyl acetate and water; the solvent system of the compound shown in the formula V comprises dichloromethane, water and methanol, wherein the volume ratio of the dichloromethane to the water to the methanol is 1:1:1.
CN202111616319.3A 2021-12-27 2021-12-27 Compound and application thereof in serving as or preparing ABCG2 agonist Active CN116354912B (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104069145A (en) * 2014-06-04 2014-10-01 苏州大学 Application of lindley eupatorium herb in preparing anti-hepatitis B virus medicaments

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104069145A (en) * 2014-06-04 2014-10-01 苏州大学 Application of lindley eupatorium herb in preparing anti-hepatitis B virus medicaments

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Jun Huo等.Cytotoxic Sesquiterpene Lactones from Eupatorium lindleyanum.《J. Nat. Prod.》.2004,第第67卷卷第1470-1475页. *
鄢贵龙等.高速逆流色谱法分离野马追乙酸乙酯萃取物中三种倍半萜烯内酯.《淮阴师范学院学报(自然科学版)》.2012,(第2012年03期期),261-265. *

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